Peramivir is a member of a class of antiviral agents that work by inhibiting viral neuraminidase, an enzyme essential for the influenza virus to replicate and infect its hosts. In addition to influenza A and B, avian influenza virus (H5N1) has been shown to be sensitive to peramivir. More specifically, depending on the influenza strain, peramivir has been determined to be 2 to 10 times more potent as a neuraminidase inhibitor than oseltamivir (Tamiflu®) and zanimivir, based on experimentally determined concentrations of each required for 50% inhibition of neuraminidase activity in vitro.
It has been reported that studies in rodents and primates have established the safety and efficacy of intramuscular injection of peramivir in a mouse influenza model. Further intravenous and intramuscular formulations of peramivir are reported to have been evaluated in pre-clinical animal models with success. However, human studies with oral forms of peramivir have demonstrated very poor oral bioavailability of peramivir. In particular it has been reported that in a phase III clinical trial of an oral formulation of peramivir, the antiviral activity against influenza A and B did not reach statistical significance.
Accordingly there is a need for neuraminidase inhibitor compositions which exhibit improved bioavailability and efficacy when administered orally for treatment or prevention of influenza infections.